Chronic infection with HCV is common, affecting up to 1% of the UK population, and the World Health Organisation (WHO) estimated that more than 200 million people globally are infected with HCV. It is well recognised that chronic HCV infection is associated with a wide variety of symptoms including fatigue, upper abdominal pain and dyspepsia, which lead to an overall reduction in the quality of life. Conventional therapy with pharmaceutical agents leads to the reduction of viral load but is effective in only about 40% of patients. There is thus a need for effective treatments that can reduce the symptoms associated with HCV infection and thereby improve the quality of life of a greater percentage of chronic hepatitis C (CHC) patients.
Furthermore there is a need for products that will target (and inhibit the activity of) the causative virus with less side effects.
In applicant's international application WO2005079823 there is disclosed a four herb combination product which in addition to providing symptomatic relief had been shown, by way of a replicon assay, to exhibit anti-HCV activity (inhibition of 41.8%) at a dilution of 1/350.
The product is composed of four herbal extracts and is formulated as follows:
Herbal Extracts:
Milk Thistle Fruit dry extract0.200 gChinese Sage Root dry extract0.225 gSchisandra Fruit dry extract0.400 gAstralagus Root dry extract0.585 gExcipients:
Macrogol 6000 powder0.600 gFerwogel 30.385 (molecular weight0.070 g3.5-4.0 × 106)Mannitol EZ0.160 gAerosil 2000.050 gAspartame0.050 gCaramel powder0.100 gPeppermint powder aroma0.060 g
The applicant has investigated this product further and has surprisingly discovered that an anti-HCV activity appears to derive from only one plant, demonstrating both good activity and no detectable cell cytotoxicity. That plant is Astragalus, and it has further been determined that a fraction purified by a factor of greater than 10, more particularly greater than 50, more particularly still greater than 75 and most particularly between 75 and 200 is particularly active.
The active fraction can be produced in good yield in effectively a three stage process comprising:                I. an alcoholic extraction (which may be repeated);        II. an ethanol-water precipitation process (which may be repeated); and        III. a systematic solvent fractionation step with a plurality of solvents of different polarity.        
Preferably, the systematic solvent fractionation utilizes a number of different solvents commencing with the least polar and finishing with the most polar. The active fraction is a dichloromethane fraction or a solvent with similar polarity.
The active fraction (and sub-fractions) can be characterized with reference to one or more markers, one or a combination of which may be responsible for the anti-HCV activity and polymerase inhibition. Particular markers identified include:                Astragaloside I,        Formononetin-7-O-β-D-glucoside; and        3′-hydroxyl-formononetin-7-O-β-D-glucoside.        
Additionally they can be identified by way of TLC fingerprints as set out in the detailed description.
The plant which exhibits the activity is a member of the Leguminosae family, more particularly huang qi:
Pharmaceutical name: Radix Astragali Membranaceous;
Botanical name: Astragalus membranaceus (Fisch) Bge. or Astragalus membranaceus Bge var. Mongholicus Hsiao (hereafter Astragalus).
The plant may be referred to as Milkvetch in Europe and it is the root which is used.
In traditional Chinese herbal medicine a dosage (based on dry raw material) of 9-30 g and occasionally up to 60 g is used. Typically it is taken as a decoction. According to Pharmacopoeia of the People's Republic of China (English Edition 2000) Vol I a cold water extraction method gives a water soluable extractive of not less than 17%.
According to Chinese Herbal Medicine, Materia Medica, Revised edition, chemically the root of Astragalus membranaceus is known to contain, as major ingredients, D-β asparagine, 2′4′-dihydroxy-5,6-dimethoxyisoflavane, calycosin, formononetin, cycloastragenol, astragalosides, choline, betaine, kumatakenin, sucrose, glucuronic acid and β-sitosterol.
It's chemical constituents are discussed further in Chinese Drugs of Plant Origin, Springer-Verlag which further discusses it's pharmacology and the symptomatic relief in the treatment of chronic hepatitis.
According to Chang H M and But P P (1987) Pharmacology and applications of Chinese Materia Medica (Vol ii) World Scientific Publishing, Astragalus membranaceus may enhance immunological function. More particularly reference is made to the use of a 100% decoction, 0.4 ml daily, to “protect” the liver and a clinical trial in which Huangqi injection achieved normalization of GPT levels in 80% of patients. (This is a symptomatic treatment.)
None of the referenced documents or other published literatures teaches the use of a single herb Astragalus, or a defined fraction thereof, as an antiviral in the treatment of hepatitis C.
Additional prior art identified includes:
CN1616097 which discloses a lozenge containing attenuated Newcastle disease virus vaccine or deactivated Newcastle disease virus vaccine, 10-120 hemagglutination units, astragalus root 1-20000 mg, liquiritigenin 1-1000 mg, supplementary material and stabilizer. It is stated to be suitable for preventing SARS and other viral infectious respiratory tract diseases and to have auxiliary treatment effects on hepatitis B and C.
CN1607003 which discloses the use of a composition comprising Chinese caterpillar fungus (50-90 parts) with astragalus root (10-50 parts) as an auxiliary therapeutic agent for hepatitis C. It is stated to adjust immune function and improve curative effect.
US2005/0074428 which discloses an adjuvant agent for use in combination with interferon and ribivarin for treating Hepatitis C containing 50-90 wt % cordyceps sinensis and 10-50 wt % astragalus memsrancens.
CN 1448163 which discloses a Chinese recipe comprising astragalus root among some eleven herbs to treat various diseases including hepatitis C.
CN1393255 which discloses a nineteen herb mix including astragalus root for treating hepatitis C.
CN1593586 which discloses a pill for treating hepatitis C comprising at least 15 herbs, one of which is raw astragalus root.
US2005/0147699 which discloses the use of an astragalus radix and codonopsis pilosulae radix mixed extract for inhibiting carcinogenesis and metastasis. It states that Astragalus is recorded, in the traditional pharmacopea, to treat chronic nephritis, albuminuria, myositis, antihypertensive, coronary artery disease, cerebral infarction, peptic ulcer (duodenal and gastric ulcer), renal disease and diabetes mellitus. It makes no reference to its potential use as an anti viral agent.
Indeed none of the documents suggests that a single herb Astragalus extract can be used alone as an antiviral to treat hepatitis, particularly hepatitis C.